Prepotent response inhibition and reaction times in children with attention deficit/hyperactivity disorder from a Caribbean community

Impairment in inhibitory control has been postulated as an underlying hallmark of attention deficit/hyperactivity disorder (ADHD), which can be utilized as a quantitative trait for genetic studies. Here, we evaluate whether inhibitory control, measured by simple automatized prepotent response (PR) inhibition variables, is a robust discriminant function for the diagnosis of ADHD in children and can be used as an endophenotype for future genetic studies. One hundred fifty-two school children (30.9% female, 67.8% with ADHD) were recruited. The ADHD checklist was used as the screening tool, whilst the DSM-IV Mini International Neuropsychiatry Interview, neurologic interview and neurologic examination, and the WISC III FSIQ test were administered as the gold standard procedure to assert ADHD diagnosis. A Go/No-Go task using a naturalistic and automatized visual signal was administered. A linear multifactor model (MANOVA) was fitted to compare groups including ADHD status, age, and gender as multiple independent factors. Linear discriminant analysis and the receiver operating characteristic curve were used to assess the predictive performance of PR inhibition variables for ADHD diagnosis. We found that four variables of prepotent response reaction time- and prepotent response inhibition established statistically significant differences between children with and without ADHD. Furthermore, these variables generated a strong discriminant function with a total classification capability of 73, 84% specificity, 68% sensitivity, and 90% positive predictive value for ADHD diagnosis, which support reaction times as a candidate endophenotype that could potentially be used in future ADHD genetic research.     

Adult attention deficit hyperactivity disorder: translating research into practice

Attention deficit hyperactivity disorder (ADHD) in adults is a prevalent, yet under-appreciated, under-researched and poorly understood condition. Given this, it is imperative that information and awareness regarding this condition are made more widespread, both amongst the general public and amongst healthcare professionals. Further, given our poor understanding of the aetiology of the condition, meaningful translational research that migrates into and better informs clinical practice must be a priority. In this brief review we highlight areas regarding the clinical diagnosis and management of ADHD in adults (guidelines, rating scales, pharmacotherapy, psychotherapy) as well as areas of promising translational research (genetics, neuroimaging, sleep and circadian rhythms, animal models of ADHD). We address some of the challenges presented for both clinicians and healthcare providers and research scientists working to improve the lives of those adults with ADHD.     

Attention-deficit/hyperactivity disorder and alexithymia: a pilot study

Although the relationship between alexithymia and psychopathology has been studied extensively in adults, research is lacking on alexithymia in childhood psychopathology. The aim of this study was to investigate the relationship between alexithymia and attention-deficit/hyperactivity disorder (ADHD). The Italian version of the Alexithymia Questionnaire for Children was administered to a sample of 50 children with a DSM-IV diagnosis of ADHD, as assessed by means of the K-SADS PL, and to 100 healthy, age- and sex-matched children without ADHD. The total alexithymia score as well as the difficulty in identifying feelings (DIF) and externally oriented thinking factors were significantly associated with ADHD. The total alexithymia score, the DIF, and the difficulty in describing feelings factors were also significantly associated with symptoms of hyperactivity/impulsivity. No significant relationship between alexithymia and inattentiveness symptoms emerged. Results provide preliminary data on the relationship between alexithymia and ADHD. Findings point to an association between difficulty in identifying emotions and hyperactivity/impulsivity. Future studies conducted on larger patient samples, as well as longitudinal designs, are warranted to confirm our findings.     

Retrospective assessment of childhood ADHD symptoms for diagnosis in adults: validity of a short 8-item version of the Wender-Utah Rating Scale

The Wender-Utah Rating Scale (WURS) is a widely used self-report instrument for retrospective assessment of childhood ADHD. However, many WURS items are not specific to ADHD. Here, we investigated the effect of excluding these items on the performance of the WURS in predicting adult ADHD based on previous diagnosis and current clinically significant symptoms. The study was conducted on a sample of adults (n = 1014; 48 % male) participating in a family-based investigation of ADHD. Participants completed the 61-item WURS questionnaire and the 66-item Conners Adult ADHD Rating Scale. Receiver operating characteristic (ROC) curves were used to compare the performance of the eight-item WURS (WURS-8) and the longer WURS-25 in predicting previous ADHD diagnosis and current clinically significant ADHD symptoms. WURS-8 and WURS-25 have approximately the same power to predict adult ADHD, based on either previous diagnosis or current symptoms (area under the ROC curves >0.8). WURS-8 performs at least as well as the longer WURS-25 in predicting adult ADHD. This 8-item questionnaire is thus a valid instrument and is especially useful for screening for ADHD in large epidemiological samples.     

Socioeconomic Associations with ADHD: Findings from a Mediation Analysis

Background

Children from disadvantaged socioeconomic backgrounds are at greater risk of a range of negative outcomes throughout their life course than their peers; however the specific mechanisms by which socioeconomic status relates to different health outcomes in childhood are as yet unclear.

Aims

The current study investigates the relationship between socioeconomic disadvantage in childhood and attention deficit/hyperactivity disorder (ADHD), and investigates putative mediators of this association in a longitudinal population-based birth cohort in the UK.

Methods

Data from the Avon Longitudinal Study of Parents and Children was used (n = 8,132) to explore the relationship between different measures of socioeconomic status at birth-3 years and their association with a diagnosis of ADHD at age 7. A multiple mediation model was utilised to examine factors occurring between these ages that may mediate the association.

Results

Financial difficulties, housing tenure, maternal age at birth of child and marital status were significantly associated with an outcome of ADHD, such that families either living in financial difficulty, living in council housing, with younger or single mothers’ were more likely to have a child with a research diagnosis of ADHD at age 7. Financial difficulties was the strongest predictor of ADHD (OR 2.23 95% CI 1.57-3.16). In the multiple mediation model, involvement in parenting at age 6 and presence of adversity at age 2-4 mediated 27.8% of the association.

Conclusions

Socioeconomic disadvantage, conceptualised as reported difficulty in affording basic necessities (e.g. heating, food) has both direct and indirect impacts on a child’s risk of ADHD. Lower levels of parent involvement mediates this association, as does presence of adversity; with children exposed to adversity and those with less involved parents being at an increased risk of having ADHD. This study highlights the importance of home and environmental factors as small but important contributors toward the aetiology of ADHD.     

Stigma in attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a frequently diagnosed disorder in child- and adulthood with a high impact affecting multiple facets of social life. Therefore, patients suffering from ADHD are at high risk to be confronted with stigma, prejudices, and discrimination. A review of the empirical research in the field of ADHD with regard to stigma was performed. The findings of investigations in this field were clustered in different categories, including stigma in children with ADHD, stigma in adults with ADHD, stigma in relatives or in people close to a patient with ADHD, and the influence of stigma on authorities' attitudes toward patients with ADHD. Variables identified to contribute to stigma in ADHD are public's uncertainty concerning the reliability/validity of an ADHD diagnosis and the related diagnostic assessment, public's perceived dangerousness of individuals with ADHD, socio-demographical factors as age, gender, and ethnicity of the respondent or the target individual with ADHD, stigmatization of ADHD treatment, for example public's skepticism toward ADHD medication and disclosure of diagnostic status as well as medication status of the individual with ADHD. The contribution of stigma associated with ADHD can be conceptualized as an underestimated risk factor, affecting treatment adherence, treatment efficacy, symptom aggravation, life satisfaction, and mentally well-being of individuals affected by ADHD. Public as well as health professionals' concepts about ADHD are highly diverse, setting individuals with an ADHD diagnosis at greater risk to get stigmatized.     

ADHD in adults: a concept in evolution

Although attention-deficit/hyperactivity disorder (ADHD) has been recognized as a disorder affecting individuals across the life cycle since the end of the nineties, there is still considerable debate on how to conceptualize the disorder in adults, and on the best way to operationalize diagnostic criteria for this age range. In this comprehensive non-systematic review of the literature, we provide data about prevalence and presentation of ADHD in adulthood as well as discuss major problems in applying criteria developed for children in assessing adults (clinical utility, threshold of symptoms for diagnosis, full ADHD diagnosis in childhood, information source, and additional dimensions for diagnosis-executive functioning impairment and emotional impulsivity). In addition, we provide some recommendations for improving ADHD diagnostic criteria in adulthood.     

ADHD and autism: differential diagnosis or overlapping traits? A selective review

According to DSM-IV TR and ICD-10, a diagnosis of autism or Asperger Syndrome precludes a diagnosis of attention-deficit/hyperactivity disorder (ADHD). However, despite the different conceptualization, population-based twin studies reported symptom overlap, and a recent epidemiologically based study reported a high rate of ADHD in autism and autism spectrum disorders (ASD). In the planned revision of the DSM-IV TR, dsm5 (www.dsm5.org), the diagnoses of autistic disorder and ADHD will not be mutually exclusive any longer. This provides the basis of more differentiated studies on overlap and distinction between both disorders. This review presents data on comorbidity rates and symptom overlap and discusses common and disorder-specific risk factors, including recent proteomic studies. Neuropsychological findings in the areas of attention, reward processing, and social cognition are then compared between both disorders, as these cognitive abilities show overlapping as well as specific impairment for one of both disorders. In addition, selective brain imaging findings are reported. Therapeutic options are summarized, and new approaches are discussed. The review concludes with a prospectus on open questions for research and clinical practice.     

Factors predicting treatment adherence in patients with adult attention-deficit/hyperactivity disorder: a preliminary study

This study aimed to elicit patient- and treatment-related factors that can potentially predict treatment adherence in adult ADHD. Subjects who were over 18 and received a diagnosis of ADHD were included in the study. Chart review data of 102 subjects regarding demographics, medications, comorbidities, concomitant medications and domains of functional impairment were collected, and predictors were assessed using a binominal logistical regression model. One hundred and two patients (78.4 % male) with a mean age of 28.8 (SD = 9.8, range = 18–55) years were enrolled in the study. Childhood diagnosis of ADHD, agents used for treatment (MPH or atomoxetine), individual domains of dysfunction and use of additional psychotropic drugs were not found to be related to treatment adherence. Patients with a university education and those referred for family history of ADHD were more likely to adhere to treatment (p = 0.05 and 0.03, respectively). On the other hand, reasons for referral other than ADHD were significantly more frequently related to non-adherence (p = 0.02). Treatment noncompliance remains a significant problem despite therapeutic effects of medications. Identification of predictors of non-adherence can lead to heightened awareness of special populations at risk. We have found that prior awareness on ADHD (via past history/media/friends) leading to self/clinician referral to rule out ADHD and pervasiveness of symptoms across functional domains led to better compliance in our sample. Future research with prospective design utilizing objective tools for adherence is required.     

ADHD in acute care psychiatric inpatients

Attention-deficit hyperactivity disorder (ADHD) is a neurocognitive disorder characterized by symptoms of inattention, impulsivity and motor hyperactivity. The worldwide prevalence of ADHD, in the general adult population, has been estimated to be 2.8%. Patients with ADHD have a high incidence of comorbidity with other psychiatric disorders. Those with a psychiatric disorder as well as ADHD have more psychosocial difficulties than those without ADHD. Despite knowing that ADHD is often comorbid with other psychiatric diagnoses, there are currently no studies elucidating the prevalence of ADHD in the inpatient psychiatric population, nor is there significant information about its impact. The lack of research into this topic suggests more needs to be done in the field of adult ADHD, especially in the inpatient psychiatric population and with respect to impairment in patient function. Knowing the prevalence of ADHD and its impact on quality of life in adult inpatients will help lay the groundwork for effective screening and management. The purpose of this study was to understand the prevalence rates of ADHD among psychiatric acute care inpatients. Other objectives included comparing the quality of life and functioning between patients with a primary psychiatric diagnosis and ADHD (treated or untreated) versus those with a primary psychiatric diagnosis and no ADHD. Thirty-three (N = 31) psychiatric inpatients were screened using the Adult ADHD Self-Report Scale. Those that screened positive for ADHD received a full diagnostic assessment for ADHD. All patients completed the Weiss Functional Impairment Rating Scale (WFIRS) to assess level of functioning and a Clinical Global Impression of Severity/Improvement Scale (on admission and discharge). Demographic information was also obtained. Of the 31 patients analyzed, 12 had a diagnosis of ADHD (36.4%). The participants diagnosed with ADHD scored significantly higher on the WFIRS, suggesting decreased functioning compared to patients without comorbid ADHD. Patients with ADHD also scored significantly higher in the individual domains of this rating scale, suggesting impairment in family, work and social functioning as well as decreased life-skills, poor self-concept and increased risk-taking behavior. In this sample, the prevalence of ADHD is significantly higher among acute care psychiatric inpatients than in the general population. Patients with concomitant ADHD suffer more functional impairment than those without. These findings merit further investigation into the value of routine screening and patient-specific treatment of ADHD in this patient population.     

注意缺陷多动障碍共患阅读障碍：认知-脑-基因的多维度研究进展

注意缺陷多动障碍（Attention-Deficit/Hyperactivity Disorder, ADHD）和发展性阅读障碍（Developmental Dyslexia, DD）是两种常见的神经发育性障碍,二者共患的比率高达25%～48%。本文拟从认知-脑-基因等多个维度对ADHD共患DD的研究进展进行综述。ADHD和DD共患的共同认知损害可能是加工速度缺陷,其作为内表型能够很好的帮助解释遗传因素如何通过影响认知功能进而导致出现ADHD共患DD的临床表型。而国内对ADHD共患DD的研究较少,已有的多项研究仅关注ADHD伴学习障碍,但缺乏标准的DD临床诊断标准。本文指出了统一诊断标准、结合多学科研究以及未来个体化训练的必要性。     

Neurodevelopmental disorders: Metallomics studies for the identification of potential biomarkers associated to diagnosis and treatment

BackgroundDiagnosis and treatment of complex diseases such as Neurodevelopmental Disorders (NDDs) can be resolved through the identification of biomarkers. Metallomics (research on biometals) and metallomes (metalloproteins/metalloenzymes/chaperones) along with genomics, proteomics and metabolomics, can contribute to accelerate and improve this process.AimThis review focused on four NDDs pathologies (Schizophrenia, SZ; Attention Deficit Hyperactivity Disorder, ADHD; Autism, ADS; Epilepsy), and we reported, for the first time, different studies on the role played by the principal six essential trace elements (Cobalt, Co; Copper, Cu; Iron, Fe; Manganese, Mn; Selenium, Se; Zinc, Zn) that can influence diagnosis/treatment.Resultsin light of the literature presented, based on meta-analyses, we suggest that Zn (glutamatergic neurotransmission, inflammation, neurodegeneration, autoimmunity alterations), could be a potential diagnostic biomarker associated to SZ. Moreover, considering the single association studies going in the same direction, increased Cu (catecholamine alterations, glucose intolerance, altered lipid metabolism/oxidative stress) and lower Fe (dopaminergic dysfunctions) levels were associated with a specific negative symptomatology. Lower Mn (lipid metabolism/oxidative stress alterations), and lower Se (metabolic syndrome) were linked to SZ. From the meta-analyses in ADHD, it is evidenced that Fe (and ferritin in particular), Mn, and Zn (oxidative stress dysfunctions) could be potential diagnostic biomarkers, mainly associated to severe hyperactive or inattentive symptoms; as well as Cu, Fe, Zn in ADS and Zn in Epilepsy. Fe, Zn and Mn levels seem to be influenced by antipsychotics treatment in SZ; Mn and Zn by methylphenidate treatment in ADHD; Cu and Zn by antiepileptic drugs in Epilepsy.ConclusionsAlthough there is controversy and further studies are needed, this work summarizes the state of art of the literature on this topic. We claim to avoid underreporting the impact of essential trace elements in paving the way for biomarkers research for NDDs.     

A pilot study: differential effects of methylphenidate-OROS on working memory and attention functions in children with attention-deficit/hyperactivity disorder with and without behavioural comorbidities

To examine the effects of methylphenidate-OROS (MPH-OROS) on working memory (WM) and attention functions in children with attention-deficit hyperactivity disorder (ADHD), and to investigate whether there is a differential effect in ADHD children with (ADHD+) and without (ADHD-) behavioural comorbidities. Participants included a clinic referred sample of 12 stimulant na?ve school-aged children with a diagnosis of combined ADHD according to the DSM-IV criteria (6 ADHD+, 6 ADHD-), and 11 healthy children. A neuropsychological protocol was applied at three different moments: before treatment, after one those of MPH-OROS, and after one month of MPH-OROS daily treatment. The protocol was simultaneously administered to the control group. Initial differences in attention parameters between na?ve children with ADHD and the control group disappeared after the first dose of MPH-OROS. For WM, one month of daily treatment was necessary to achieve this pattern of results. Both ADHD groups (ADHD+ and ADHD-) showed these differences, but there was a greater improvement in (ADHD-). MPH-OROS had an immediate effect on attention deficits, but long-term treatment was needed to improve WM to the level of healthy subjects. The presence of comorbid behavioural conditions determined a less robust response in neuropsychological performance to stimulant treatment.     

Omega-3 fatty acids are inversely related to callous and unemotional traits in adolescent boys with attention deficit hyperactivity disorder

A number of research studies have reported abnormal plasma fatty acid profiles in children with ADHD along with some benefit of n?3 to symptoms of ADHD. However, it is currently unclear whether (lower) long chain-polyunsaturated fatty acids (LC-PUFAs) are related to ADHD pathology or to associated behaviours. The aim of this study was to test whether (1) ADHD children have abnormal plasma LC-PUFA levels and (2) ADHD symptoms and associated behaviours are correlated with LC-PUFA levels. Seventy-two, male children with (n=29) and without a clinical diagnosis of ADHD (n=43) were compared in their plasma levels of LC-PUFA. Plasma DHA was higher in the control group prior to statistical correction. Callous–unemotional (CU) traits were found to be significantly negatively related to both eicosapentaenoic acid (EPA), and total omega-3 in the ADHD group. The findings unveil for the first time that CU and anti-social traits in ADHD are associated with lower omega-3 levels.     

Diagnosing and treating attention-deficit/hyperactivity disorder in adults

Adult attention deficit/hyperactivity disorder (ADHD) is a valid and impairing psychiatric disorder. In this article, we review the diagnosis of ADHD in adults, focusing on symptom presentation differences between pediatric and adult ADHD as well as the importance of assessing functional impairments. Differentiating ADHD from other clinical disorders is often the most difficult part of making an ADHD diagnosis in adults. Psychiatric comorbidities are also described and discussed as potential impact factors upon not only diagnosing ADHD but also treatment of adult ADHD. Especially in those adults with psychiatric comorbidities, treatments need to be multimodal and include both pharmacotherapy and psychosocial interventions.     

Toward a better understanding of ADHD: LPHN3 gene variants and the susceptibility to develop ADHD

During the past 15 years, an impressive amount of genetic information has become available in the research field of psychiatry, particularly as it relates to attention-deficit/hyperactivity disorder (ADHD). However, the classical clinical approach to ADHD has minimally affected and not significantly been improved by this genetic revolution. It is difficult to predict how long it will take for genetic findings to alter the way clinicians treat patients with ADHD. New medications or treatment protocols may take years to become routine clinical practice. However, when taken together, recent successes in genomics, pharmacogenomics, and genetic epidemiology have the potential (1) to prevent comorbid consequences of ADHD, (2) to individualize therapies for patients with ADHD, and (3) to define new epidemiological policies to aid with the impact of ADHD on society. Here, we present an overview of how genetic research may affect and improve the quality of life of patients with ADHD: as an example, we use the discovery of LPHN3, a new gene in which variants have recently been shown to be associated with ADHD.     

Neurofeedback: An Alternative and Efficacious Treatment for Attention Deficit Hyperactivity Disorder

Current research has shown that neurofeedback, or EEG biofeedback as it is sometimes called, is a viable alternative treatment for Attention Deficit Hyperactivity Disorder (ADHD). The aim of this article is to illustrate current treatment modalities(s), compare them to neurofeedback, and present the benefits of utilizing this method of treatment to control and potentially alleviate the symptoms of ADHD. In addition, this article examines the prevalence rates and possible etiology of ADHD, the factors associated with ADHD and brain dysfunction, the current pharmacological treatments of ADHD, Ritalin, and the potential risks and side effects. Behavior modification and cognitive behavioral treatment for ADHD is discussed as well. Lastly, a brief history of the study of neurofeedback, treatment successes and clinical benefits, comparisons to medication, and limitations are presented.     

Role of Dopamine Receptors in ADHD: A Systematic Meta-analysis

The dopaminergic system plays a pivotal role in the central nervous system via its five diverse receptors (D1-D5). Dysfunction of dopaminergic system is implicated in many neuropsychological diseases, including attention deficit hyperactivity disorder (ADHD), a common mental disorder that prevalent in childhood. Understanding the relationship of five different dopamine (DA) receptors with ADHD will help us to elucidate different roles of these receptors and to develop therapeutic approaches of ADHD. This review summarized the ongoing research of DA receptor genes in ADHD pathogenesis and gathered the past published data with meta-analysis and revealed the high risk of DRD5, DRD2, and DRD4 polymorphisms in ADHD.     

Appropriateness of array‐CGH in the ADHD clinics: A comparative study

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorder with a worldwide prevalence of about 5%. The disorder is characterized by inattentive, hyperactive and impulsive behavior and is often comorbid with other neuropsychiatric conditions. Array comparative genomic hybridization (array‐CGH) testing has been proved to be useful to detect chromosomal aberrations in several neuropsychiatric conditions including autism spectrum disorders (ASD) and intellectual disability (ID). The usefulness of array‐CGH in the ADHD clinics is still debated and no conclusive evidence has been reached to date. We performed array‐CGH in 98 children and adolescents divided in two similarly sized groups according to the clinical diagnosis: (a) one group diagnosed with ADHD as primary diagnosis; (b) the other group in which ADHD was co‐morbid with ASD and/or ID. We detected pathogenetic and likely pathogenetic copy number variants (CNVs) in 12% subjects in which ADHD was co‐morbid with autism and/or intellectual disability and in 8.5% subjects diagnosed with ADHD as primary diagnosis. Detection of CNVs of unknown clinical significance was similar in the two groups being 27% and 32%, respectively. Benign and likely benign CNVs accounted for 61% and 59.5% in the first and second group, respectively. Differences in the diagnostic yield were not statistically significant between the two groups (P > .05). Our data strongly suggest that array‐CGH (a) is a valuable diagnostic tool to detect clinically significant CNVs in individuals with ADHD even in the absence of comorbidity with ASD and/or ID and (b) should be implemented routinely in the ADHD clinics.